Fingolimod in Schizophrenia Patients (STEP)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Indiana University
Sponsor:
Information provided by (Responsible Party):
Nikki Mehdiyoun, Indiana University
ClinicalTrials.gov Identifier:
NCT01779700
First received: January 11, 2013
Last updated: September 3, 2014
Last verified: September 2014
  Purpose

This will be a single site safety and proof of concept study conducted at the Indiana University Psychotic Disorders Program. Forty subjects with schizophrenia or schizoaffective disorders will be randomized 1:1 to double-blind treatment with fingolimod or matched placebo for duration of 8 weeks.


Condition Intervention Phase
Schizophrenia
Drug: Fingolimod
Drug: placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Fingolimod in Schizophrenia Patients Who Have Suboptimal Responses to Antipsychotic Drug Treatment

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • Dosing Safety [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    assess the effects of dosing fingolimod in subjects with schizophrenia who are concomitantly being treated with antipsychotic drugs on ECG and laboratory


Secondary Outcome Measures:
  • Cognition, including executive functioning, verbal fluency, attention, task switching, and motor speed [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    assessment of the effects of fingolimod versus placebo on cognition measures above as determined by BACS and Trails B scores

  • verbal memory [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    assessment of the effects of fingolimod versus placebo on cognition measures above as determined by BACS and Trails B scores as well as encoding and recognition tasks within the MRI protocol

  • Positive and Negative Symptoms of Schizophrenia [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    assessment of the effects of fingolimod versus placebo on positive and negative symptoms as determined by the PANSS total score

  • plasma cytokines [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    assessment of the effects of fingolimod versus placebo on plasma cytokine levels

  • working memory [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    assessment of the effects of fingolimod versus placebo on cognition measures above as determined by BACS and Trails B scores as well as encoding and recognition tasks within the MRI protocol

  • DTI-derived FA [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    assessment of the effects of fingolimod versus placebo on DTI-derived FA and other MRI indices


Estimated Enrollment: 40
Study Start Date: January 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Fingolimod
0.5mg of fingolimod, oral administration, daily, for 8 weeks.
Drug: Fingolimod
0.5mg each day of 8 week cycle
Other Name: gilenya
Placebo Comparator: placebo
placebo, oral administration, daily, for 8 weeks.
Drug: placebo
1 tablet each day of 8 week cycle
Other Name: sugar pill

Detailed Description:

Study Design This will be a single site safety and proof of concept study conducted at the Indiana University Psychotic Disorders Program. Forty subjects with schizophrenia or schizoaffective disorders will be randomized 1:1 to double-blind treatment with fingolimod or matched placebo for duration of 8 weeks.

All subjects will be admitted to the Indiana Clinical and Translational Sciences Institute Clinical Research Center (CRC) and remain hospitalized for the first 24 (+/- 2) hours post initial dose of study medication. The CRC is located in Indiana University Hospital and has 24 hour staffing with nurses skilled in conducting Phase 1 and Phase 2 investigational drug studies.

Background and Rationale Schizophrenia is a severe brain disorder that begins during the teenage years and early twenties and typically progresses to a life-long chronic illness marked by psychotic symptoms, cognitive impairment and poor functioning. A leading hypothesis to account for the symptoms and cognitive dysfunction of this disorder is that abnormalities exist in cortical circuits, particularly in frontal and temporal areas. An interest in cortical circuitry has led to a focus on the integrity of cortical white matter tracts as possibly contributing to the pathophysiology of this illness. Indeed, several lines of evidence have supported abnormalities in white matter structure and function in schizophrenia. Numerous myelin-related genes and their functional expression have been associated with schizophrenia. Moreover, quantitative and qualitative abnormalities in prefrontal cortical oligodendrocytes have been found in postmortem studies. MRI-determined volumetric reductions in prefrontal white matter have been reported in schizophrenia. Advances in MRI technology have enhanced the ability to study white matter pathology in vivo. Diffusion tensor imaging (DTI) and fractional anisotropy (FA) provides an assessment of the density and integrity of white matter tracts. Decreased FA has been reported in many de-myelinating diseases including multiple sclerosis (MS), leukodystrophies, and HIV. Numerous studies using DTI have reported decrements in FA in schizophrenia with the most consistent abnormalities occurring in frontal cortical white matter. Also, FA has been shown to be sensitive to therapeutic drug effects in MS which supports DTI-derived FA as an outcome measure in clinical trials of neuroprotective agents.

Fingolimod (FTY720, approved as Gilenya™ ) is a sphingosine-1-phosphate (S1P) receptor modulator and recently licensed in the USA and several other countries for relapsing forms of multiple sclerosis (MS). It is administered as a once per day oral preparation. In registration clinical trials, it had positive effects on brain atrophy, MRI-determined axonal lesions and relapse rates. Significant improvement in the mean number of MRI assessed T1 gadolinium (Gd) enhanced lesions/patient and the percentage of patients free of T1 Gd-enhanced lesions was observed within 6 months of treatment and there was evidence of clinical improvement as early as 2 months after treatment initiation

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion

  • 18 to 65 yrs, able to give informed consent
  • DSM IV-TR Diagnosis of schizophrenia or schizoaffective disorder
  • Previous and/or current exposure to 2 antipsychotic medications (> 4 weeks in duration and > FDA approved therapeutic range for schizophrenia)
  • willing to participate in a minimum of 1 day of hospitalization
  • Clinical stability:

    1. CGI-S score of < 4 at randomization AND
    2. no exacerbation of illness within 4 weeks prior to randomization, leading to an intensification of psychiatric care in the opinion of the investigator AND
    3. antipsychotic treatment stability for at least 4 weeks prior to randomization
  • Female subjects of childbearing potential must test negative for pregnancy at screening and agree to use a single, effective, medically acceptable method of birth control for the duration of the study and for two months following cessation of study medication
  • Subjects must agree not to consume tonic water for the duration of the study and for two months following cessation of study medication
  • Sub-optimally treated positive OR negative symptoms as defined by the Brief Psychiatric Rating Scale (BPRS):

    1. BPRS positive symptom factor (conceptual disorganization, hallucinations, suspiciousness, unusual thought content) score of > 4 on any one item or a sum > 8 on the factor
    2. BPRS negative symptom factor (motor retardation, blunted affect, inappropriate affect) score of > 4 on any one item or a sum > 6 on the factor

Exclusion

  • Subjects who are considered prisoners per the IU Standard Operating Procedures for Research Involving Human Subjects
  • current acute, serious, or unstable medical conditions
  • Clinically significant electrocardiogram abnormality: corrected QT interval >450 msec (M) or >470 msec (F) prior to randomization OR sinus bradycardia (HR < 50 beats/min)
  • Subjects who have experienced the following within the six months prior to study entry: myocardial infarction, unstable angina, stroke, transient ischemic attach (TIA), decompensated heart failure requiring hospitalization or Class III/IV heart failure
  • hypokalemia, hypomagnesemia, or congenital long-QT syndrome
  • known HIV+ status
  • active seizure disorder
  • Pregnant or lactating women or women who plan to become pregnant or will be lactating within two months after cessation of study drug
  • Implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS unit, ventriculoperitoneal shunt, or other contraindication to undergoing an MRI scan
  • class1a or class 3 antiarrhythmic agents, beta blockers, diltiazem, verapamil, digoxin, tricyclic antidepressants, warfarin, ketoconazole, ketamine
  • Subjects likely to need a live attenuated vaccine during the course of the study or within two months after stopping study medication
  • Subjects with no history of chicken pox or chicken pox vaccination, or with a negative VZV titer
  • Active herpes simplex outbreak, mononucleosis, or zoster
  • Subjects with histories of ischemic heart disease, myocardial infarction, congestive heart failure, cardiac arrest, cerebrovascular disease, unexplained or recurrent syncope, cardiac conduction prolongations (prolonged P-R interval), cardiac arrhythmias, symptomatic bradycardia, or severe untreated sleep apnea
  • antineoplastic, immunosuppressive, or immune modulating therapies
  • history of macular edema or uveitis
  • Known IQ < 70
  • current active fungal or viral infection
  • Current DSM IV-TR diagnosis of substance dependence (excluding caffeine and nicotine)
  • Positive urine toxicology screen for the following: cocaine, benzodiazepines, barbiturates, methamphetamine, opiate, methadone, phencyclidine, or amphetamine prior to randomization
  • Test positive for (1) Hep C virus antibody, (2) Hep B surface antigen (HBsAg) with or without positive Hep B core total antibody, (3) HIV 1 or 2 antibodies, or (4) Mantoux tuberculin test.
  • moderate to severe renal impairment as defined by creatinine clearance < 60 ml/min at screening
  • hepatic impairment as defined by liver transaminases or total bilirubin > 3 × upper limit of normal
  • Subjects considered a high risk for suicidal acts - active suicidal ideation OR any suicide attempt in 90 days prior to screening
  • Subjects who have participated in a clinical trial with any pharmacological treatment intervention for which they received study-related medication in the 4 weeks prior to screening OR Subjects currently receiving treatment (within 1 dosing interval + 4 weeks) with an investigational depot formulation of an antipsychotic medication
  • Subjects who demonstrate overtly aggressive behavior or who are deemed to pose a homicidal risk in the investigator's opinion
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01779700

Contacts
Contact: Nikki Mehdiyoun, MA 317-941-4287 iupdp@iupui.edu
Contact: Natalie Case, MS 317-941-4287 iupdp@iupui.edu

Locations
United States, Indiana
Center for NeuroImaging Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Nikki Mehdiyoun, MA    317-941-4287    iupdp@iupui.edu   
Sub-Investigator: Andrew Saykin, PsyD         
Sub-Investigator: Brenna McDonald, PsyD         
Sub-Investigator: Yang Wang         
Sub-Investigator: John West         
Sub-Investigator: Daniel Westfall, BS         
Larue D Carter Memorial Hospital Recruiting
Indianapolis, Indiana, United States, 46222
Contact: Nikki Mehdiyoun, MA    317-941-4287    iupdp@iupui.edu   
Contact: Natalie Case, MS    317-941-4287    iupdp@iupui.edu   
Principal Investigator: Alan Breier, MD         
Sub-Investigator: Emily Liffick, MD         
Sub-Investigator: Alexander Radnovich, MD, PhD         
Sub-Investigator: Nikki Mehdiyoun, MA         
Sub-Investigator: Fred Malloy, MD         
Sub-Investigator: Natalie Case, MS         
Sub-Investigator: Jenifer Vohs, PhD         
Sub-Investigator: Megan Gaunnac, BS         
Sub-Investigator: Steven M Lindgren, BS         
Sub-Investigator: Joshua Goergen, MD         
Sub-Investigator: Matthew Runyan, MD         
Sub-Investigator: Venkat Polavarapu, MD         
Sub-Investigator: Amy Visco, BS         
Sub-Investigator: Amanda Roebel, MS         
Prevention and Recovery Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Nikki Mehdiyoun, MA    317-630-6046    iupdp@iupui.edu   
Contact: Teresa Kulig, MS    317-630-6046    iupdp@iupui.edu   
Sub-Investigator: Teresa Kulig, MS         
Sub-Investigator: David Spradley, RN         
Sub-Investigator: Michael Francis, MD         
Sub-Investigator: Carol Ott, PharmD         
Sub-Investigator: Emmalee Metzler         
Sub-Investigator: Tom Hummer, PhD         
Sub-Investigator: Joan Showalter, MS         
Sponsors and Collaborators
Indiana University
Investigators
Principal Investigator: Alan Breier, MD Indiana University
Principal Investigator: Emily Liffick, MD Indiana University
  More Information

Additional Information:
No publications provided

Responsible Party: Nikki Mehdiyoun, Clinical Study Coordinator, Indiana University
ClinicalTrials.gov Identifier: NCT01779700     History of Changes
Other Study ID Numbers: 11T-001
Study First Received: January 11, 2013
Last Updated: September 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Indiana University:
psychosis
schizophrenia
cognition
fingolimod

Additional relevant MeSH terms:
Schizophrenia
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Fingolimod
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014